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Howard H. Chen, PhD


Overview

Research Interests Dr. Chen’s research focuses on the molecular imaging of cell death and survival pathways in the heart in vivo. Cell death is the hallmark of many devastating disorders including cardiovascular diseases. The ability to preserve cell viability during cardiovascular diseases is thus of utmost importance. Dr. Chen’s laboratory takes an interdisciplinary approach encompassing fundamental molecular and cellular biology, biochemistry, and state-of-the-art imaging technologies, nanoscience, and synthetic chemistry to gain biological and pathophysiological insights. His lab aims to a) develop molecular imaging probes suitable for systemic delivery in vivo, to classify cell death and survival processes. In particular, his lab focuses on the molecular imaging of autophagy, a catabolic cellular process that has been shown to be either beneficial or detrimental in cardiovascular diseases. Understanding the pathophysiological impact of autophagy and elucidating the associated changes in cell energetics, mitochondria dynamics, and metabolism thus can enhance therapeutics. b) To engineer a special class of theranostics through chemical modifications. Theranostics are imaging agents with dual therapeutic and diagnostic capabilities. Developing theranostics would allow us to see disease processes non-invasively in the body, simultaneously apply therapeutics at the site of injury, and receive real-time readout of response to treatment through imaging. c) To fully realize the potential of molecular imaging in the translational and clinical realms, Dr. Chen’s lab aims to profile structure-function relationship to optimize imaging probes suitable for clinical translation. He combines mathematical modeling and precise nanoscale characterizations to investigate probe-cell interactions both at the cellular levels and systemic analysis in vivo. This enables rational design of imaging agents that reach the target sites efficiently, is cleared readily systemically, allowing sensitive molecular imaging to be performed with minimal perturbation of the normal biological function or physiology.
Training + Education Boston College; Harvard Medical School
Gender Male
Language(s) Mandarin, Taiwanese

Honors + Awards

2012, Young Investigator Award Finalist, World Molecular Imaging Congress
2007, 2011-2013, Travel Awards, American Aging Association & World Molecular Imaging Congress
2007, Supplemental Research Grant Award, Boston College
2007, M. Shahabuddin Memorial Award, Boston College
2005, Ellison Medical Foundation Scholarship, Marine Biological Laboratory
2005, Donald J. White Teaching Excellence Award, Boston College

Publications + National Presentations

1. Chen HH, Waghorn PA, Wei L, Tapias LF, Schühle DT, Rotile NJ, Jones CM, Looby RJ, Zhao G, Elliot J, Probst CK, Mino-Kenudson M, Lauwers GY, Tager A, Tanabe KK, Lanuti M, Fuchs BC, Caravan P. Molecular magnetic resonance imaging of oxidized collagen quantifies fibrogenesis in mouse models of pulmonary and hepatic fibrosis. JCI Insights. 2017;2(11). pii: 91506

2. Chen HH, Yuan H, Cho H, Feng Y, Ngoy S, Kumar ATN, Liao R, Josephson L, Sosnovik DE. Theranostic nucleic acid binding nanoprobe exerts anti-inflammatory and cytoprotective effects in ischemic injury. Theranostics. 2017;7(4):814-825

3. Chen HH, Yuan H, Cho H, Sosnovik DE, Josephson L. Cytoprotective nanoparticles by conjugation of a polyhis tagged annexin v to a nanoparticle drug. Nanoscale. 2015;7:2255-2259

4. Zou L, Chen HH, Li D, Xu G, Feng Y, Chen C, Wang L, Sosnovik DE, Chao W. Imaging lymphoid cell death in vivo during polymicrobial sepsis. Crit Care Med. 2015;43(11):2303-2312

5. Sosnovik DE, Mekkaoui C, Huang S, Chen HH, Dai G, Stoeck CT, Ngoy S, Guan J, Wang R, Kostis WJ, Jackowski MP, Wedeen VJ, Kozerke S, Liao R. Microstructural impact of ischemia and bone marrow-derived cell therapy revealed with diffusion tensor magnetic resonance imaging tractography of the heart in vivo. Circulation. 2014;129:1731-1741

6. Chen HH, Mekkaoui C, Cho HS, Ngoy S, Marinelli B, Waterman P, Nahrendorf M, Liao R, Josephson L, Sosnovik DE. Molecular Imaging of Rapamycin-Induced Autophagy In Vivo with Probe Based Sensor, Circulation: Cardiovascular Imaging. 2013; 6(3):441-447

7. Yuan H, Cho H, Chen HH, Panagia M, Sosnovik DE, Josephson L. Fluorescent and Radiolabeled Triphenylphosphonium Probes for Imaging Mitochondria, Chemical Communications. 2013; 49(88):10361-10363

8. Chen HH, Yuan H, Josephson L, Sosnovik DE. Theranostic Imaging of the Kinases and Proteases that Modulate Cell Death and Survival. Theranostics. 2012;2(2):148-155

9. Chen HH, Feng Y, Zhang M, Chao W, Josephson L, Shaw SY, Sosnovik DE. Protective Effect of the Apoptosis-Sensing Nanoparticle AnxCLIO-Cy5.5. Nanomedicine: Nanotechnology, Biology and Medicine. 2012;8(3):291-298

10. Huang S, Chen HH, Yuan H, Dai G, Schuhle DT, Mekkaoui C, Ngoy S, Liao R, Caravan P, Josephson L, Sosnovik DE. Molecular MRI of Acute Necrosis with a Novel DNA-Binding Gadolinium Chelate. Circulation: Cardiovascular Imaging. 2011;4(6):729-737

View all Dr. Chen’s publications on PubMed:

Biography

Dr. Chen is passionate about interdisciplinary research that leads to deeper molecular understanding, and impacts human health. His research is collaborative, interfaces with physician scientists, biologists, chemists, physicists, mathematicians, and engineers. During his postdoctoral training in both the cardiology and radiology departments at Massachusetts General Hospital, Harvard Medical School, he investigated cardiovascular diseases with molecular imaging technology. Previously during his doctoral training at Boston College, Dr. Chen created a library of recombinant inbred C. elegans strains. Using genetic mapping strategies, he elucidated how the allelic interactions among naturally-occurring single nucleotide polymorphisms (SNPs) contribute to a diverse phenotype including lifespan extension and resistance to oxidative stress.

His current research focuses on developing molecular imaging contrast agents to investigate cell death processes, namely apoptosis, necrosis and autophagy in the in vivo environment. He reported, for the first time, the ability to image autophagy activation in a living mouse heart with ischemia-reperfusion injury. Through imaging, he also demonstrated that the autophagy activation is cardioprotective, reducing both cardiomyocyte cell death and final infarct size. The molecular imaging toolbox developed further allows the complex interplay among cell death pathways to be studied in vivo.

He also applied molecular imaging to study inflammation and fibrogenesis with targeted gadolinium (Gd) chelates. The targeted Gd chelates rely on fundamental chemical reactions between the probes and the targeted ligands activated during the disease processes. Once bound, the probe gives off a magnetic signature, allowing the perturbed microenvironment of the diseased organ to be investigated in vivo by molecular Magnetic Resonance imaging. The detection is non-invasive, quantitative, and amendable to longitudinal serial imaging to track disease progression and treatment response. The imaging probes are designed based on clinically approved contrast agents and are cleared readily from the body and with well-established biosafety profile. Multiplexed imaging of cell death, inflammation and fibrosis can provide invaluable insights into disease processes and tissue repair.

To bridge molecular imaging to novel therapeutics, Dr. Chen has demonstrated that several cell-death sensing nanoparticles and nanoprobes that detect cell death can also slow or prevent cell death to enhance cell survival. The dual-capability (diagnostic and therapeutic, thus theranostic) imaging probes were validated in cell culture and in mouse models with cardiac injury. The ability to image and simultaneously apply therapeutics and monitor treatment response at the molecular and cellular levels non-invasively in vivo is novel and with translational potentials.

Dr. Chen’s research employees a myriad of imaging modalities including Fluorescence tomography (FMT), Magnetic Resonance imaging (MRI), Positron Emission tomography (PET), Computed tomography (CT), and ultrasound imaging. Dr. Chen leverages the molecular imaging program towards deeper pathophysiological understanding into heart failure, cardiomyopathy, and interventional cardiology. The imaging paradigms developed and validated in preclinical animal models provide a logical route to harness molecular understanding garnered in the lab to impact disease management in the clinic.

Professional Memberships

American Heart Association
World Molecular Imaging Society

Contact Information

Phone: 617-636-8248

Molecular Cardiology Research Institute
Tufts Medical Center
800 Washington Street, Box #7703
Boston, MA 02111